POS0721 ASSOCIATION BETWEEN PRECONCEPTION COMPLEMENT LEVELS AND USE OF HYDROXYCHLOROQUINE WITH PREGNANCY OUTCOME IN PATIENTS WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME AND CARRIERS OF ANTIPHOSPHOLIPID ANTIBODIES: AN INTERNATIONAL MULTICENTER STUDY
Authors: D. Lini, C. Nalli, L. Andreoli, F. Crisafulli, M. Fredi, M. G. Lazzaroni, V. Bitsadze, A. Calligaro, V. Canti, R. Caporali, F. Carubbi, C. Chighizola, P. Conigliaro, F. Conti, C. De Carolis, T. Del Ross, M. Favaro, M. Gerosa, A. Iuliano, J. Khizroeva, A. Makatsariya, P. L. Meroni, M. Mosca, M. Padovan, R. Perricone, P. Rovere-Querini, G. D. Sebastiani, C. Tani, M. Tonello, S. Truglia, D. Zucchi, F. Franceschini, A. Tincani
Journal: Annals of the Rheumatic Diseases (2022)

Background Antiphospholipid Syndrome (APS) is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for antiphospholipid antibodies (aPL). Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and several groups investigated the significance of complement levels in human disease. C3 and C4 serum levels were assessed in several cohorts of pregnant patients with APS and/or aPL positivity in order to relate complement consumption with adverse pregnancy outcome (APO). According to some authors, hydroxychloroquine (HCQ) can control the activation of the complement system, improve pregnancy outcome and reduce aPL title. Objectives This study was designed to verify the effect of HCQ in addition to low dose aspirin (LDA) + low molecular weight heparin (LMWH) treatment in a multicenter cohort of primary APS (PAPS) and aPL carriers pregnant women and the possible correlation with preconception serum C3/C4 levels. Methods Medical records of pregnant women with confirmed positivity for aPL antibodies attending twelve referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related APO: spontaneous abortions (&lt;10 weeks of gestation), fetal loss (≥10 weeks of gestation), neonatal death (death of a formed fetus alive at birth in the first 28 days of life), preterm delivery before 37 weeks of gestation, preeclampsia, eclampsia or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet). Results We have analyzed 164 singleton PAPS/aPL carrier pregnancies (22 aPL carriers - 13%) in 128 patients: all were treated with combination therapy (LDA+LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3/C4. A triple aPL positivity was observed in 54 pregnancies, 14 of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ had not significantly improved the gestational outcome. Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3/C4 levels the addition of HCQ had not significantly improved pregnancy outcome. We have lastly evaluated 40 pregnancies with a high-risk profile (triple aPL positivity and complement consumption), in which we have found that HCQ significantly improved gestational outcome (p=0.018, Table 1). Table 1. Relationship between APO, therapy during pregnancy and risk profile. All pregnancies (n=164) Reduced C3/C4 (n=58) Triple aPL+ and reduced C3/C4 (n=40) LDA+LMWH (n, %) LDA+LMWH+HCQ (n, %) p LDA+LMWH (n, %) LDA+LMWH+HCQ p LDA+LMWH LDA+LMWH+HCQ p (n, %) (n, %) (n, %) APO 62 (46%) 16 (53%) ns 32 (68%) 4 (36%) ns 23 (77%) 3 (30%) 0.018 No APO 72 (54%) 14 (47%) 15 (32%) 7 (64%) 7 (23%) 7 (70%) Total 134 30 47 11 30 10 This observation could not be confirmed in patients with single or double aPL positivity. Conclusion The study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/PAPS high-risk patients. This observation confirms that HCQ exerts a beneficial effect on aPL pregnancies by complement inhibition as it was shown in animal models. In addition, our results provide the clinicians a useful tool to implement conventional treatment in patients at high risk of pregnancy complication or loss. References [1]De Carolis S, et al. Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment? Autoimmun Rev 2015;14:760-2. [2]Mekinian A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in antiphospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 2015;40:498-502. [3]Mekinian A et al. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? Autoimmun Rev 2015;14:23-9. Disclosure of Interests None declared